Tag Archives: health

Red Meat | The Paleo Diet
As you probably already heard, earlier this week the International Agency for Research on Cancer (IARC), which is the World Health Organization’s (WHO) cancer agency, categorized processed meat as “carcinogenic” and unprocessed red meat as “probably carcinogenic.”1 What you might not have heard is that in an accompanying Q&A document, the IARC also said, “Eating meat has known health benefits.”2

Those who read the IARC’s statement and its Q&A document are likely to conclude that this story is nowhere near as dramatic and consequential as headlines from The Guardian, The New York Times, and other news outlets have implied:

  • “Processed meats rank alongside smoking as cancer causes – WHO” – The Guardian3

  • “Meat Is Linked to Higher Cancer Risk, W.H.O. Report Finds” – The New York Times4

Let’s see what the IARC actually said, then put things in context so we can determine what it means. The IARC evaluates chemicals, pollutants, biological agents, and other substances so as to determine whether or not they are carcinogenic. Agents are classified into one of several groups, ranging from “Group 1: the agent is carcinogenic to humans,” to “Group 4: the agent is probably not carcinogenic to humans.” The IARC does not determine how much any particular agent actually increases one’s risk of getting cancer. In its own words, the IARC explains,

“The classification indicates the weight of the evidence as to whether an agent is capable of causing cancer (technically called “hazard”), but it does not measure the likelihood that cancer will occur (technically called “risk”) as a result of exposure to the agent.”5

This is an essential point. Processed meats are now grouped into the same category as cigarettes and asbestos, but this doesn’t mean the risks associated with processed meats are anywhere near those of the latter two. Cigarette smoking, for example, increases one’s relative risk of getting lung cancer by 2,500%.6 Eating processed meat, according to the IARC, increases one’s risk of getting colorectal cancer by an estimated 18%.7 Given the frequency of colorectal cancer, this means that eating 50 grams of bacon every day over the course of your life would increase your risk of getting cancer from 5% to 6%.

Missing the Big Meaty Picture

Of course, all this talk of risk misses a bigger point – context is essential. For example, will those who smoke while eating healthy diets have the same chronic disease risks as those who smoke while eating unhealthy diets? Probably not. Red meat consumed within the context of a health-supportive Paleo diet is healthy. On the other hand, red meat consumed within the context of a junk-food diet might not be healthy, especially regarding poor-quality meat.

Dr. Cordain points out, “observational studies and even randomized controlled trials typically do not control for a variety of additional elements found in feedlot-raised red meats” and “only in the past 200 years of so have we ever consumed domesticated animals fed grains, injected with hormones, antibiotics, exposed to heavy metals and pesticides and sequestered in feedlots by the hundreds of thousands.” So when someone says meat is unhealthy, we should remember that meat is not a commodity; it ranges from poor to superior quality.

The Problem with Observational Studies

To assess carcinogenicity, the IARC analyzes observational studies. As Dr. Cordain and others have repeatedly pointed out, such studies alone cannot demonstrate causality. In response to the IARC announcement, Dr. Cordain noted, “In order to establish cause and effect between diet and disease, it takes more than just observational epidemiological evidence. There must also be what is referred to as ‘biological plausibility’ in which evidence gathered from tissue, animal and short-term human metabolic studies support causality.”8, 9

With respect to unprocessed red meat, the IARC’s “probably carcinogenic” determination is not even based on strong epidemiological evidence. It’s based on “limited evidence,” which according to the IARC, “means that a positive association has been observed between exposure to the agent and cancer but that other explanations for the observations (technically termed chance, bias, or confounding) could not be ruled out.”10

So the next time your vegetarian co-worker tells you that red meat causes cancer, remember the following four rebuttals:

  1. The IARC’s classification is based on observational studies, which cannot show causality.
  2. Evidence that unprocessed red meat could be carcinogenic is based on “limited evidence,” which means confounding factors could not be ruled out.
  3. The magnitude of risk for eating processed meat (and red meat if causality could be demonstrated) is nowhere near that of established risky behaviors, like smoking.
  4. Context matters – high-quality meat is healthy within the context of healthy diets, which include plenty of vegetables and other healthy foods.

Despite all the fanfare about increased cancer risk, at least the IARC acknowledges, “Eating meat has known health benefits.” It wouldn’t have been sensational, but this should have been the headline used by major news organizations.

References

1. World Health Organization, IARC. (October 26, 2015). IARC Monographs evaluate consumption of red meat and processed meat. Press Release Number 240. Retrieved from http://www.iarc.fr/en/media-centre/pr/2015/pdfs/pr240_E.pdf

2. World Health Organization, IARC. Q&A on the carcinogenicity of the consumption of red meat and processed meat. Retrieved from http://www.iarc.fr/en/media-centre/iarcnews/pdf/Monographs-Q&A_Vol114.pdf

3. Boseley, S. (October 26, 2015). Processed meats rank alongside smoking as cancer causes – WHO. The Guardian. Retrieved from http://www.theguardian.com/society/2015/oct/26/bacon-ham-sausages-processed-meats-cancer-risk-smoking-says-who

4. O’Connor, A. (October 26, 2015). Meat Is Linked to Higher Cancer Risk, W.H.O. Report Finds. The New York Times. Retrieved from http://www.nytimes.com/2015/10/27/health/report-links-some-types-of-cancer-with-processed-or-red-meat.html

5. World Health Organization, IARC. Q&A on the carcinogenicity of the consumption of red meat and processed meat. Retrieved from http://www.iarc.fr/en/media-centre/iarcnews/pdf/Monographs-Q&A_Vol114.pdf

6. U.S. Department of Health and Human Services. (2014). The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General. Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2014.

7. World Health Organization, IARC. Q&A on the carcinogenicity of the consumption of red meat and processed meat. Retrieved from http://www.iarc.fr/en/media-centre/iarcnews/pdf/Monographs-Q&A_Vol114.pdf

8. Flegal KM. (June 1999). Evaluating epidemiologic evidence of the effects of food and nutrient exposures. Am J Clin Nutr, 69(6):1339S-1344S.

9. Potischman N, Weed DL. (June 1999). Causal criteria in nutritional epidemiology. Am J Clin Nutr, 69(6):1309S-1314S.

10. World Health Organization, IARC. Q&A on the carcinogenicity of the consumption of red meat and processed meat. Retrieved from http://www.iarc.fr/en/media-centre/iarcnews/pdf/Monographs-Q&A_Vol114.pdf

Paleo Bloggers | The Paleo Diet

INTRODUCTION

Some of the most well recognized names in the “Paleosphere” surprisingly maintain few professional, academic, or even experiential credentials which would qualify them as scientists, researchers or even lay experts in the discipline. These self proclaimed, charismatic authorities have influenced and continue to influence hundreds of thousands of people based upon nothing more than their untested subjective opinions and limited understanding of the scientific, peer review literature.

Most have never been trained in the research process, few maintain anything  more than a bare bones understanding of the scientific method and don’t have even the slightest inkling of the statistical or research design issues that can make or break the validity and generalizability of any scientific study. Universally, none of these influential Paleo bloggers have an extensive publication record in the scientific peer review literature relating to Paleo diets or anything else.

Accordingly, their blogs have no origins in their own prior refereed scientific writings (because they don’t have any).  Unfortunately, these bloggers can utter just about anything they desire about contemporary Paleo diets because virtually no objective system of checks and balances underlie their writings and opinions.

THE PEER REVIEW PROCESS

The difference between charismatic bloggers and published research scientists is that the latter must present their ideas, work and experiments before a panel of scientific peers prior to publication. The peer review process certainly is not infallible and clearly does not always insure the accuracy, generalizability or validity of any experiment or idea. Nevertheless, it generally does insure that the paper or concept has been examined by a panel of scientists and experts who usually are trained in the discipline, but who also are typically trained in universal research design and statistical concepts and procedures, without which experiments and data are meaningless and un-interpretable.

Almost universally, charismatic bloggers have little or no understanding of how research design and statistical issues can make or break the interpretation of any experiment or hypothesis, yet as I will show you they proudly offer their opinions regardless.

RESEARCH DESIGN AND STATISTICS

I graduated from the University of Utah in 1981 with a Ph.D. in Health Sciences (emphasis: Exercise Physiology).  Besides course work, one of the requirements for the Ph.D. was the successful completion of an experimental project and the subsequent write-up of this research via a Doctoral Dissertation. During my years of coursework, I took almost two quarters worth of specific graduate level classes that focused upon 1) a variety of statistical procedures, 2) research design issues, and 3) computer assisted data compilation and interpretation. Whew! These classes were not fun, and I struggled to get through some of them. But without the knowledge and experience I gained from these classes, I wouldn’t have had a clue about designing, statistically analyzing, and writing up the physiological/respiratory experiment that eventually became my Doctoral Dissertation.

When I finally completed my two year long experiment, wrote the dissertation and finally graduated, I breathed a sigh of relief in the mistaken belief that I would never again have to go through this ordeal. Wrong! At the time, little did I realize the research design, statistical and computer skills I had utilized for my Ph.D. project would never leave me, and that I would have to repeat this process again, again and again on a regular basis for the next 32 years.

It is sometimes said that the best way to better learn about any topic or skill is to have to teach it to others. As a rookie, Assistant Professor at Colorado State University in the fall of 1981, I was immediately assigned to teach a graduate course in Research Design and Statistics to both Master’s and Ph.D. students. As it turned out, I would go on to teach this course for the next 32 years, but more importantly I continually honed my research design and statistical tools not only for my own research, but also as I taught my graduate students to implement their research projects. Increasingly as my career developed I fully appreciated the magnitude of these powerful scientific tools as I served as a reviewer for scientific journal articles and governmentally sponsored grants.

“By using it, you will not lose it,” or so goes the truism.  In the case of research design and statistics, almost all charismatic bloggers, never learned these scientific tools in the first place, so their Paleo diet interpretations of the scientific literature and subsequent subjective pronouncements need to be rigorously evaluated if we are to place any credence whatsoever upon their writings.

Below are just a few key questions almost any scientist familiar with research design and statistical procedures would be able to answer. I suspect that none of our charismatic Paleo bloggers whose names you all recognize would be able to answer any of these questions off the top of their heads. Familiarity with these concepts is essential in correctly interpreting and fully understanding the scientific literature.

QUESTIONS:

  1. What is statistical power and how does it influence hypothesis testing?
  2. What is the null hypothesis. Can it be answered in either the affirmative or negative or only singly and why does it matter?
  3. What is a two-tailed statistical test? How does it affect alpha and subsequently hypothesis testing?
  4. What is the relationship between alpha (a type 1 statistical error) and beta (a type 2 statistical error) and how does sample size (n) interact with these concepts to affect hypothesis testing?
  5. Why is sample size crucial when evaluating the internal and external validity of an experiment?
  6. What are the four levels of data and how does this information influence the type of statistic to be employed in the analysis and why?
  7. What are the differences among 1) pre-experimental, 2) quasi experimental and 3) true experimental designs. How do these considerations influence internal validity and generalizability of the experiment?
  8. When is a repeated measures ANOVA used to analyze data and why should multiple t-tests not be used in making repeated comparisons?
  9. What are the differences between parametric and non-parametric statistical tests and how does the level of data influence their choice?
  10. Do descriptive statistics show causality? How about inferential statistics? What are common differences between the two?
  11. Is it possible to generate a standard deviation greater than the mean? How are large standard deviations generally interpreted with small sample sizes?  How about with large sample (n) sizes?
  12. When should the standard error of the mean (SEM) be employed in lieu of the standard deviation?
  13. With the inclusion of more and more variables into a forward, stepwise multiple regression equation, what is the effect upon “R”; what is the effect upon “p”. Why does this matter?
  14. How does the use of partial correlation techniques help to unravel relationships among a series of variables?

OK, OK – ENOUGH! You get my point; we could go on endlessly with these obscure statistical and research design concepts. For most of you, not only can you not answer these questions, the answers are irrelevant anyway.

What you want to find out from your charismatic blogger is a simple answer to a simple question – should I drink milk or not? How about kefir? Should I regularly consume legumes and beansHow about sea salt – is it OK? Do contemporary Paleo diets require supplements?

I’ll give you some insight into your charismatic blogger – off the top of their heads, without the input of skilled professionals, they could not answer these research design and statistical questions either – they simply lack the training. Like you, they are barely even familiar with these terms and concepts known to most research scientists.

Without the knowledge or understanding of research design and statistical notions our charismatic, influential Paleo bloggers simply cannot understand the subtleties, limitations and flaws in the scientific papers they may read. Accordingly, their advice and pronouncements about a variety of Paleo Diet issues are at best incomplete, and at worst flat out wrong.

CAUSE AND EFFECT

One of the challenges faced by nutritional scientists when they ultimately make recommendations regarding what we should and should not eat is to establish cause and effect between a dietary element and the subsequent development or prevention of disease. Some foods and some dietary habits promote good health whereas others promote disease. Figure 1 demonstrates the four primary procedures by which causality is established between diet and disease.1, 2

Figure 1

Figure 1. The four primary procedures by which causality is established between diet and disease.1, 2

No single procedure alone can establish cause and effect,1, 2 nor can any single study prove causality.3 Observational epidemiological studies can only show relationships among variables and are notorious for showing conflicting results4 and cannot provide decisive evidence by themselves either for or against specific hypotheses.5

For example increased animal protein has been associated with a decreased risk for coronary heart disease (CHD) in a large group of nurses (The Nurses Health Study),6 whereas exactly the opposite association was found for markers of CHD and meat consumption in people from rural China.7, 8 An analogy here may be appropriate to show you why observational epidemiological studies can only show relationships and not establish causality. In New York City, there is a strong association between the size of a structure fire and the number of fire trucks at the fire, but can we conclude that more fire trucks cause bigger fires?

In order to establish cause and effect between diet and disease, it takes more than just observational epidemiological evidence.5 There must also be what is referred to as “biological plausibility” in which evidence gathered from tissue, animal and short term human metabolic studies support causality.2 When observational epidemiological evidence is augmented by biological plausibility studies and confirmed by randomized controlled human trials, the case for causality becomes ever more convincing. Unfortunately, charismatic Paleo bloggers seem to be unaware of these basic research design parameters when they read, evaluate and report upon the scientific nutritional literature.

SUMMARY

Over the past five or six years, The Paleo Diet, has grown into a household concept known to millions of people worldwide and has beneficially affected the health and wellbeing of countless individuals. Nevertheless, the original message, developed primarily in the scientific literature, has now increasingly become diluted as certain charismatic, non-scientific bloggers turn the original concept into a non-factual, personal belief system without consensus or support by the scientific Paleo Diet literature.

If your charismatic Paleo blogger promotes any of the following nutritional guidelines below, you may want to rigorously research each of these concepts for yourself and then reconsider these so-called “experts” as spokespersons for contemporary Paleo diets.

CHARISMATIC PALEO BLOGGERS MYTHS DEBUNKED:

  1. Dairy products can be a regular components of contemporary Paleo diets.
  2. Sea salt can be used in lieu of regular table salt in contemporary Paleo diets.
  3. Legumes and beans are nutritious foods and should be regularly included in contemporary Paleo diets.
  4. Contemporary Paleo diets cannot be successfully implemented without the use of various supplements or supplement mixtures conveniently concocted and sold only by your friendly charismatic Paleo blogger.*

* Clearly humans are no longer wild hunter-gatherers and in the 21st century we are definitely operating in a foreign niche. Consequently, a few dietary exceptions are required.

  1. Most of us stay indoors in buildings 24/7, whereas our ancestors had no such thing as “indoors.” Accordingly, to insure our blood concentrations of Vitamin D are equivalent to our outdoor living ancestors, we need to either sunbathe regularly or supplement with Vitamin D.
  2.  

  3. If we eat fatty fish (salmon, herring, mackerel, sardines, etc.) 2-3 times per week, there is absolutely no need to supplement with fish oil. Nevertheless, a significant number of people in westernized countries don’t like or can’t afford fresh fish. Hence the need to supplement with fish oil, so that our blood concentrations of long chain omega 3 fatty acids are comparable to our pre-agricultural ancestors who ate the entire carcass of their prey animals (brains, gonads, liver, kidney) which are highly concentrated sources of long chain omega 3 fatty acids. For most westerners it is culturally offputting and not consistent with our modern tastes to regularly eat brains etc.
  4.  

  5. The calcium issue is a tricky whicket, but we have devoted an entire blog and soon to be peer review scientific paper on this topic: “Got Bones? The Paleo Solution for Building Strong Bones While Keeping Arteries Soft and Supple” Evolution through natural selection has completely figured out the calcium conundrum in hominins from 2 MYA until the agricultural revolution. Outdoor living in a wild environment to which we are genetically adapted solves the calcium issue. Modern people who habitually consume salt (whether Paleo or not), unless they consume fresh fruits and veggies daily to the tune of about 25-35 % of energy may require calcium supplements.

REFERENCES

  1. Sempos CT, Liu K, Ernst ND. Food and nutrient exposures: what to consider when evaluating epidemiologic evidence. Am J Clin Nutr. 1999 Jun;69(6):1330S-1338S.
  2. Potischman N, Weed DL. Causal criteria in nutritional epidemiology. Am J Clin Nutr. 1999 Jun;69(6):1309S-1314S.
  3. Freudenheim JL. Study design and hypothesis testing: issues in the evaluation of evidence from research in nutritional epidemiology. Am J Clin Nutr. 1999 Jun; 69(6): 1315S-1321S.
  4. Fraser GE. A search for truth in dietary epidemiology. Am J Clin Nutr. 2003 Sep;78(3 Suppl):521S-525S.
  5. Flegal KM. Evaluating epidemiologic evidence of the effects of food and nutrient exposures. Am J Clin Nutr. 1999 Jun;69(6):1339S-1344S.
  6. Hu FB, Stampfer MJ, Manson JE, Rimm E, Colditz GA, Speizer FE, Hennekens CH, Willett WC. Dietary protein and risk of ischemic heart disease in women. Am J Clin Nutr. 1999 Aug;70(2):221-7.
  7. Campbell TC, Junshi C. Diet and chronic degenerative diseases: perspectives from China. Am J Clin Nutr. 1994 May;59(5 Suppl):1153S-1161S.
  8. Campbell TC, Parpia B, Chen J. Diet, lifestyle, and the etiology of coronary artery disease: the Cornell China study. Am J Cardiol. 1998 Nov 26;82(10B):18T-21T.

Could Dopamine Be the Key to Health and Happiness? | Paleo

Ah, the joy of being both happy and healthy. I can bet my last dollar that many reading this would like to find the magic solution to what is for many, a far-reaching statement. While many Paleo followers can ride high on the claim of being healthy, the same cannot be said for many about being happy.

Intellectual scholars have been debating the key to happiness. Research studies found that certain neurotransmitters in the brain, such as dopamine, are key to your happiness.1 While this may sound familiar, understanding the nature in which the brain’s reward center functions will help in processing this information. A recent study conducted in London, and published in the Journal of Neuroscience expands on the role dopamine plays in happiness, as well as in the risks we take.2

OVERVIEW

In this study, 30 healthy people were given the drug levodopa, which is a treatment for Parkinson’s Disease. Levodopa (L-dopa) functions by increasing the amount of dopamine levels in the brain.3 Happiness was measured using functional MRI imagining, to show signals in the area of the brain known as the striatum. This region has substantial dopaminergic input, as a result of increased dopamine receptors.

The individuals were assigned a gambling task, where they had to make choices between safe and risky options. After each choice they were assessed on their level of happiness. In this double-blind placebo-controlled study, the individuals received both levodopa and placebo. When the individuals were given a placebo, the level of happiness was higher after receiving large rewards. On the other hand when given levodopa, the individuals exhibited high levels of happiness regardless of the type of reward, whether small or large.

UNDERSTANDING DOPAMINE

Dopamine is a natural chemical produced in the areas of the brain known as the substantia nigra and the ventral tegmental.4 Dopamine not only affects the brain’s reward center, but when you walk and talk, it is the proper balance of dopamine levels in your brain that also controls these functions. An imbalance of dopamine can result in disorders where, for example, patients with the neurological disorder Parkinson’s Disease do not have enough, meanwhile scientists hypothesize excess dopamine can cause schizophrenia.5 Research has also shown an association between drugs that increase dopamine, and addictive behaviors like an increased appetite for food and alcohol.2

PLEASURE CONTROLS

Research shows the presence of dopamine during an imagined event, affects the brain’s expectation of how enjoyable that event will be in the future.5 In order words, make sure your dopamine levels are in check when you’re planning out your next workout or healthy meal. You’ll be pumped for the fun ahead!

PALEO FOODS TO BOOST DOPAMINE PRODUTION

Interestingly enough, research has also shown there are decreased dopamine receptors in overweight individuals.6 Paleo followers can attest that many who adopt a Paleo diet not only see the pounds fall away, but the robust volume of scientific literature also shows how it decreases the risk for the many chronic diseases that plague western civilizations.

There are foods that help in naturally increasing dopamine levels in our brain. Dopamine comes from the amino acid tyrosine. Foods rich in tyrosine include avocados and almonds.7 These foods also contain high levels of antioxidants, are great sources of natural fat, and are no stranger to Paleo dieters. Other foods include eggs, pork, fish, nuts and seeds.8 Just when you thought you knew all the benefits of eating Paleo!

SUMMARY

When you eat right, you win. Stick to Paleo foods rich in tyrosine, lead an active lifestyle, and keep your happiness and health in check. Keep the brain active by solving puzzles, painting, or crafting; all shown to increase dopamine levels.9 While there is no magic solution, there is a scientific backing which works.

 

REFERENCES

[1] Cloud, J. (2009, November 27). Can Dopamine Make Your Future Look Brighter? Retrieved September 15, 2015, from Time: http://content.time.com/time/health/article/0,8599,1943224,00.html

[2] Rutledge, R., Skandali, N., Dayan, P., & Dolan, R. (2015). Dopaminergic modulation of decision making and subjective well-being. Journal of Neuroscience, 35, 9811-9822.

[3] Mayo Clinic. (2015). Retrieved Sep 15, 2015, from Carbidopa, Entacapone, And Levodopa (Oral Route): http://mayoclinic.org/drugs-supplements/carbidopa-entacapone-andl-levodopa-oral-route/before-using/drg-20061604

[4] Rutledge, R., Skandali, N., Dayan, P., & Dolan, R. (2015). Dopaminergic modulation of decision making and subjective well-being. Journal of Neuroscience, 35, 9811-9822.

[5] Cloud, J. (2009, November 27). Can Dopamine Make Your Future Look Brighter? Retrieved September 15, 2015, from Time: http://content.time.com/time/health/article/0,8599,1943224,00.html

[6] DOE/Brookhaven National Laboratory. (2007). Retrieved September 15, 2015, from ScienceDaily: http://sciencedaily.com/releases/2007/10/071025091036.htm

[7] University of Maryland Medical Center. (2013, July 16). Tyrosine. Retrieved September 15, 2015, from https://umm.edu/health/medical/altmed/supplement/tyrosine

[8] http://nutritiondata.self.com/

[9] Wilson, J. (2015, January 5). This is your brain on crafting. Retrieved September 15, 2015, from CNN: http://www.cnn.com/2014/03/25/health/brain-crafting-benefits/

Carnitine Levels and Muscle Boosters | The Paleo Diet
When we follow a healthy, Paleo diet, we want to make sure we’re covering all bases, not only in terms of getting every last vitamin and mineral, but doing so in a balanced way. As such, entertaining the idea of taking supplements to meet recommended daily value (DV) requirements is natural. In fact, so many of us take supplements that we’re spending billions.

Sales of supplements in 2013 reached $13 billion, as more people turned to the supplements to boost their health and lose weight, despite an investigation that found most didn’t contain herbs listed on their labels, and in some cases, the supplements didn’t even identify potentially dangerous allergens.1

So, do we really need any of them? Doesn’t a real Paleo diet provide all we need? Yes, but there are a couple caveats worth considering including supplementation for:

VITAMIN D

Most westerners, particularly those living at northern latitudes, do not receive sufficient sunlight exposure required for our bodies to produce adequate blood concentrations of vitamin D.

FISH OIL

We could avoid supplementing if we were to eat the entire carcass of animals and fish (brains, liver, marrow, gonads) which are rich sources of EPA and DHA.2

In my experience, I’ve found on an individual basis, clients may need supplements of one kind or another, but rather than going to the nearest Whole Foods and dropping hundreds of dollars in self-diagnosed natural remedies, do yourself a favor and if you feel something is amiss, see your functional medicine doctor3 to get a full work up and determine what you actually need.

What’s the deal with some of the popular supplements that we see advertised all over the place? We already know how to address some of them. Our need for calcium, for example, is adequately met on a Paleo diet, even though we don’t eat dairy.

And, rather than turning to B12 supplements for energy, we can create a naturally balanced blood sugar levels simply by following the low-glycemic eating regime that is inherent to Paleo.

But what about some of the more confusing supplements, such as those designed to help with performance in sport? Carnitine is a perfect example.

L-carnitine is an amino acid that is naturally produced in the body.  Supplements are used to increase levels in people whose natural level of L-carnitine is too low because they have a genetic disorder, are taking certain drugs, or because they are undergoing a medical procedure that uses up the body’s L-carnitine. It is also used as a replacement supplement in strict vegetarians, dieters, and low-weight or premature infants.4

But can it also give us an edge in sport? Apparently so, according to a recent study published in Cell Metabolism.

“Supplementation with carnitine increases activity of metabolic pathways that helped mice run longer and further than those without supplementation”, said the US-based researchers who conducted a recent study focused on an enzyme, which uses carnitine to boost energy economy.5

Researchers moved to address ways routine activities like mowing the lawn or climbing stairs was becoming problematic due to exercise intolerance. The study concluded that carnitine supplementation did, in fact, work synergistically with the enzyme to optimize energy metabolism during exercise.

But what were the subjects eating? There’s no mention of the diet administered to the mice in the study, and aside from a brief mention that “nutritional and/ or pharmalogical strategies aimed at promoting enzymatic activity could prove useful for offsetting metabolic inertia,” we’re left with a fundamental piece of information, which seems to have been grossly overlooked.

Meat, poultry, and fish, staples of any Paleo diet, are all rich sources of L-carnitine where 63% – 75% is absorbed, whereas only 14% – 20% is absorbed in supplementation.6 Rather than heading straight to the vitamin shop and stocking up on carnitine, do yourself and your wallet a favor and make sure your diet is, in fact, a balanced Paleo approach. L-Cartinine supplementation may prove to be nothing more than the proverbial Band-Aid.

 

REFERENCES

[1] “Americans Are Ignoring the Science and Spending Billions on Dietary Supplements.” Washington Post. The Washington Post, 04 Feb. 2015. Web

[2] “Nutrient Deficiencies and Supplementation | The Paleo Diet.” The Paleo Diet. N.p., 23 Feb. 2015. Web

[3] “Institute for Functional Medicine What Is Functional Medicine?” Institute for Functional Medicine What Is Functional Medicine

[4] “L-carnitine: Uses, Side Effects, Interactions and Warnings – WebMD.” WebMD. WebMD, n.d. Web. 29 July 2015.

[5] Carnitine Supplementation Could Boost Muscle Stamina: Animal Data.” NutraIngredients.com. N.p., n.d. Web.

[6] Linus Pauling Institute. “L-Carnitine.” Micronutrient Information Center. Oregon State Univeristy, 2015. Web.

5 Paleo Diet Habits To a New You in a New Year | The Paleo Diet

The New Year is full of possibilities, opportunities and time. We embrace its distant horizon with arms wide-open, full of energy, desire and passion to achieve our goals. The goals start out as resolutions and seem to fall by the wayside by the time Valentine’s Day rolls around.  Resolutions to lose weight, to manage money better, to make more time for you, to get that promotion, to workout regularly, to eat healthy always.

The challenge with New Years resolutions is exactly that – it’s a resolution.  An intention to do something new from that day forward, or a firm decision to break a habit that’s likely become a routine. With such a concrete approach, the second you falter, it all too quickly just too far out of reach to accomplish in the year. Maybe next year. Well, giving up or making concessions just isn’t our style!

Set yourself up for success this year and try making five small changes to your habits rather than committing to tall-order resolutions. When you set realistic expectations of yourself, it’s much easier to hold yourself accountable, but more importantly get you on track towards those big ticket New Year’s resolutions.

1. Eat Organ Meats Once a Week

Yes I’m talking about Liver (Chicken, Beef), Giblets (Chicken, Turkey), Kidney, Beef Tongue and if you’re feeling ready – Heart. Organ meats have been eaten for centuries and contain more nutrients and minerals than any other meat1. BONUS: they’re almost always cheaper than other meats, so you can save a few bucks as well. Two resolutions in one – this year’s starting out great already!

2. Wash and Prep Your Vegetables

Do this as soon as you get home from the grocery store.  Why unload all the groceries from your reusable bags, into the fridge, and then take it all out again to wash, cut, dice, and slice. Save yourself the time and get them ready when you get home. This will make cooking time shorter, and you have healthy snacks ready to go whenever you might need to grab them or munch on them at home. Time management, healthy snacking. Check, check.

3. Double the Recipe

When you’re cooking dinner, double all the ingredients as if you’re cooking for more than yourself, your partner or the family.  When you’re ready to serve, grab a sealable glass container (or two) and dish out dinner for it as well. Let it cool at room temperature and store in the fridge. This guarantees you’ve got something nutritious to take for lunch to work the next day, or a ready to go home cooked meal when you need it most.  The trick is to not eat it just because its there when you’re eating dinner!

4. Get the Tech out of Your Bedroom

TVs, iPods, laptops, tablets, cell phones. Out. This will likely be the biggest change and toughest habit to break, but it’s so worth it! Sleep REM cycles are impacted from light pollution at night and have serious adverse effect on health2.  We’ve all experienced irritability, inability to focus and exhaustion from a lack of sleep. Why purposely make it difficult for our brain and body to get the rest it needs to perform best?

5. Add Turmeric to your Spice Cabinet

This is the simplest habit to add and it’s full of health benefits.  Turmeric has been used as an anti-inflammatory for centuries in Asian culture, and recently been linked to decreased symptoms of IBS.3 Turmeric has strong antioxidant properties and is easy to add to any recipe – why not give our Dried Lime Chicken a try! With just a pinch of turmeric you’ll release a burst of flavor and a delectable golden punch to your dish. Keep it next to the pepper and add to soups, stews, salads, marinades, even smoothies.

And just like that you’re making a few small changes (five to be exact) to get healthy, eat better, get more sleep, have more free time and even save some money along the way. Just think, this might be the best year yet.

Happy 2015!

@PaleoWired
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Sanja JovanovicSanja Jovanovic is a co-founder of PALEO WIRED – a site dedicated to GATHER the best and latest paleo recipes & information to share with you, to inspire you to EAT the deliciousness of those recipes and creations and to REPEAT each day.  Because we’re all going to eat something anyway, might as well make it something that our bodies will thank us for!

References

[1] Wahls, Terry, Adamson, Eve. The Wahls Protocol: How I Beat Progressive MS Using Paleo Principles and Functional Medicine. New York: Penguin Group; 2014. 432 p.

[2] Cho JR1, Joo EY, Koo DL, Hong SB. Let there be no light: the effect of bedside light on sleep quality and background electroencephalographic rhythms. Sleep Med. 2013 Dec;14(12):1422-5. PMID: 24210607.

[3] McCann MJ, Johnston S, Reilly K, Men X, Burgess EJ, Perry NB, Roy NC. The effect of turmeric (Curcuma longa) extract on the functionality of the solute carrier protein 22 A4 (SLC22A4) and interleukin-10 (IL-10) variants associated with inflammatory bowel disease. Nutrients. 2014 Oct 13;6(10):4178-90. PMID: 25314644.

You Are When You Eat | The Paleo Diet

You don’t have to be on the Paleo Diet for long to start noticing extravagantly packaged, brightly colored foods that weren’t part of our Paleolithic past. But with all the time we spend explaining that hunter-gatherers didn’t eat Big Macs and jelly beans, we sometimes forget that these foods aren’t the only unnatural consequence of our modern lifestyle. Just fly across five or six time zones to see how ill equipped your body is to handle time change. As fit as our Paleolithic ancestors were, they were never able to run quite fast enough to experience jet lag.

Our bodies are, in fact, directed by circadian rhythms that dictate when we are active, when we sleep, and even when we eat. Modern conveniences such as artificial lighting and always-within-reach snacks may disturb these rhythms placing additional evolutionary stress on our bodies that ultimately affects our diet and our health. At least this is the theory presented in a recent review published in the Proceedings of the National Academy of Science by Dr. Mark Mattson et al. These researchers proposed that our health isn’t just about what we eat, but when we eat.1

Natural 24-hour rhythms permeate the entire animal and even the vegetable kingdoms.2,3 In humans, circadian oscillations have been found in over 10% of our expressed genes affecting almost all of our bodies’ metabolic, neurological and endocrine pathways.4The suprachiasmatic nucleus (SCN) in the hypothalamus acts as our “master clock,” responding to daily light-dark cycles through photoreceptive ganglion cells in our retinas.5

Mattson et al. questioned whether the invention of artificial light and shift work perturbed this circadian clock, promoting longer daily cycles of consumption (especially nighttime meals.)

In turn, our erratic eating behaviors affect our biological clocks. Two of the main pathways in our bodies that respond to fasting and feeding – cAMP response element binding protein (CREB) for fasting and the insulin-dependent mammalian target of rapamycin (MTOR) for feeding – can directly influence circadian oscillations. In one mouse study, researchers were able to use feeding to rapidly shift liver oscillations 10 hours out of sync with the light-sensitive SCN.6

This cycle of altered eating behavior and perturbed rhythms building on one another may be a major cause of obesity and metabolic disturbances.

Which raises the question, if our natural eating pattern has been altered, is the daily western habit of three square meals truly a healthy lifestyle or a consequence of disturbed rhythms? Does it actually contribute to unnecessary metabolic stress?7-10

Recent reports of hunter-gatherer eating behavior and Dr. Cordain’s own ethnographic research paint the picture of a very different eating cycle. One of hunter-gatherers consuming a single large meal in the late afternoon or evening after spending the day hunting and gathering on little to no food.11, 12 Nor did hunter-gatherers eat consistently day-to-day. While anthropological research has debunked the notion of intermittent starvation in Paleolithic times,13 without the modern joys of a stocked fridge and preservative-packed foods, hunter-gatherers likely had frequent days of severely reduced energy intake.

So if three daily large meals puts us at evolutionary odds, how should we eat?

The health benefits of a calorie restricted (CR) diet, including a positive effect on longevity, have already been established.14-17 In their review, Mattson et al. go a step further proposing two timing-dependent variations on a CR diet that are more consistent with Paleolithic behavior and may actually enhance the health benefits.18

The first is a time-restricted feeding (TRF) diet where consumption is limited to a short period during the day – a four to eight hour window – to better match life before artificial lighting. The second was intermittent energy restriction (IER) consisting of periodic days where calories are greatly reduced (i.e. just 500 calories) such as twice per week – an eating pattern that would be more consistent with a Paleolithic lifestyle. Examples of both diets are shown in the figure below:

Circadian Rhythms | The Paleo Diet

Mattson, M.P., et al., Meal frequency and timing in health and disease. Proc Natl Acad Sci U S A, 2014. 111(47): p. 16647-53.

More and more studies are touting the health benefits of IER, but studies of TRF are less promising, often finding no benefits over a standard calorie restricted diet.19,20 Mattson et al. found four potential explanations for why an IER diet prevents and even reverses a variety of chronic diseases including cancer, CVD, diabetes and neurodegenerative diseases.21

Better “Stress” Management

IER creates a mild stress in our bodies. But instead of being damaging, it may spark an adaptive response that ultimately enhances our defense mechanisms against more serious stress. A variety of animal studies have supported this claim showing that alternate day fasting can prevent age-related decline in the antioxidant enzymes superoxide dismutase I and catalase and can protect and even strengthen neurons against oxidative, metabolic, and proteotoxic damage.22

Improved Bioenergetic Profile

A three meal-per-day paradigm has a consequence of maintaining elevated blood sugar and insulin levels both of which have been shown to have multiple health consequences including obesity, diabetes and a variety of metabolic disorders.25-28Due to extended periods of fasting, both IER and TRF diets improve metabolic profiles including lower blood concentrations of sugar, insulin and leptin, increased insulin sensitivity, better mobilization of fatty acids, and elevated ketones which can promote neuron health and protect against cancer.18, 29,30 The figure below shows improved insulin sensitivity and blood triglyceride concentrations on an IER diet over even a daily CR diet.

Circadian Rhythms | The Paleo Diet

Harvie, M.N., et al., The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women. Int J Obes (Lond), 2011. 35(5): p. 714-27.

Reduced Inflammation

More and more research is revealing that almost all chronic diseases are linked to inflammation both locally and throughout the body. An IER diet reduces key inflammatory markers such as TNF-α and IL-6.31 However, Mattson et al. were uncertain whether the diet had a direct effect on inflammation or if it was a side effect of the weight loss typically associated with the diet.

Improved Repair and Maintenance

Damaged organelles and misfolded proteins are a natural consequence of daily living. Fortunately our cells have mechanism, such as autophagy to take up and remove damaged cellular material. Inhibition of autophagy may accelerate aging.32Eating puts the body in a protein building mode which suppresses autophagy.33Extended periods of fasting allow our cells to switch gears and cleanse themselves.

Meal timing is a promising area of research that can bring us one step closer to eating like our Paleolithic ancestors. However, even the authors of the review pointed out that long term controlled studies are still limited and there is no consensus yet on how to best implement an IER diet. A healthy Paleo Diet should still focus primarily on what you eat. But even if you don’t want to try a timing-dependent variation, it might be worth questioning whether 9:00 pm is the best time to eat baked salmon or if you really need that big a bowl of fruit and almonds every morning.

Thanks for reading!

Trevor Connor | The Paleo DietTrevor Connor is Dr. Cordain’s last mentored graduate student and will complete his M.S. in HES and Nutrition from the Colorado State University this year and later enter the Ph.D. program. Connor was the Principle Investigator in a large case study, approximately 100 subjects, in which he and Dr. Cordain examined autoimmune patients following The Paleo Diet or Paleo-like diets.

REFERENCES

[1]Mattson, M.P., et al., Meal frequency and timing in health and disease. Proc Natl Acad Sci U S A, 2014.111(47): p. 16647-53.

[2]Reppert, S.M. and D.R. Weaver, Coordination of circadian timing in mammals. Nature, 2002. 418 (6901): p. 935-41.

[3]Goodspeed, D., et al., Postharvest circadian entrainment enhances crop pest resistance and phytochemical cycling. Curr Biol, 2013.23 (13): p. 1235-41.

[4]Panda, S., J.B. Hogenesch, and S.A. Kay, Circadian rhythms from flies to human. Nature, 2002. 417 (6886): p. 329-35.

[5]Hatori, M. and S. Panda, The emerging roles of melanopsin in behavioral adaptation to light. Trends Mol Med, 2010.16 (10): p. 435-46.

[6]Stokkan, K.A., et al., Entrainment of the circadian clock in the liver by feeding. Science, 2001. 291(5503): p. 490-3.

[7]Liu, Z., et al., PER1 phosphorylation specifies feeding rhythm in mice. Cell Rep, 2014.7(5): p. 1509-20,

[8]Hatori, M., et al., Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab, 2012. 15(6): p. 848-60.

[9]Garaulet, M., et al., Timing of food intake predicts weight loss effectiveness. Int J Obes (Lond), 2013. 37(4): p. 604-11.

[10]Vanitallie, T.B., Sleep and energy balance: Interactive homeostatic systems. Metabolism, 2006. 55 (10 Suppl 2): p. S30-5.

[11]Hill, K. and A.M. Hurtado, Aché life history : the ecology and demography of a foraging people. Foundations of human behavior. 1996, New York: Aldine de Gruyter. xix, 561 p.

[12]Berbesque, J.C., et al., Hunter-gatherers have less famine than agriculturalists. Biol Lett, 2014. 10 (1): p. 20130853.

[13]Cordain, L., J. Miller, and N. Mann, Scant evidence of periodic starvation among hunter-gatherers. Diabetologia, 1999. 42(3): p. 383-4.

[14]Fontana, L. and S. Klein, Aging, adiposity, and calorie restriction. JAMA, 2007. 297 (9): p. 986-94.

[15]Das, U.N., When less is adequate: protein and calorie restriction boosts immunity and possibly, longevity–but how and why? Nutrition, 2009. 25(9): p. 892-5.

[16]Yuan, Y., et al., Enhanced energy metabolism contributes to the extended life span of calorie-restricted Caenorhabditis elegans. J Biol Chem, 2012. 287(37): p. 31414-26.

[17]Blagosklonny, M.V., Calorie restriction: decelerating mTOR-driven aging from cells to organisms (including humans). Cell Cycle, 2010. 9 (4): p. 683-8.

[18]Harvie, M.N., et al., The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women. Int J Obes (Lond), 2011. 35 (5): p. 714-27.

[19]Stote, K.S., et al., A controlled trial of reduced meal frequency without caloric restriction in healthy, normal-weight, middle-aged adults. Am J Clin Nutr, 2007.85 (4): p. 981-8.

[20]Carlson, O., et al., Impact of reduced meal frequency without caloric restriction on glucose regulation in healthy, normal-weight middle-aged men and women. Metabolism, 2007. 56(12): p. 1729-34.

[21]Longo, V.D. and M.P. Mattson, Fasting: molecular mechanisms and clinical applications. Cell Metab, 2014. 19 (2): p. 181-92.

[22]Pieri, C., et al., Food restriction in female Wistar rats: V. Lipid peroxidation and antioxidant enzymes in the liver. Arch Gerontol Geriatr, 1992. 14 (1): p. 93-9.

[23]Mattson, M.P., Energy intake and exercise as determinants of brain health and vulnerability to injury and disease. Cell Metab, 2012. 16 (6): p. 706-22.

[24]Marosi, K. and M.P. Mattson, BDNF mediates adaptive brain and body responses to energetic challenges. Trends Endocrinol Metab, 2014. 25 (2): p. 89-98.

[25]Dandona, P., A. Aljada, and A. Bandyopadhyay, Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol, 2004. 25 (1): p. 4-7.

[26]Mehran, A.E., et al., Hyperinsulinemia drives diet-induced obesity independently of brain insulin production. Cell Metab, 2012.16 (6): p. 723-37.

[27]Brand-Miller, J.C., et al., Glycemic index and obesity. Am J Clin Nutr, 2002. 76(1): p. 281S-5S.

[28]Wang, J., et al., Overfeeding rapidly induces leptin and insulin resistance. Diabetes, 2001. 50 (12): p. 2786-91.

[29]Johnson, J.B., et al., Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma. Free Radic Biol Med, 2007. 42 (5): p. 665-74.

[30]Lee, C., et al., Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy. Sci Transl Med, 2012. 4 (124): p. 124ra27.

[31]Kroeger, C.M., et al., Improvement in coronary heart disease risk factors during an intermittent fasting/calorie restriction regimen: Relationship to adipokine modulations. Nutr Metab (Lond), 2012. 9 (1): p. 98.

[32]Rubinsztein, D.C., G. Marino, and G. Kroemer, Autophagy and aging. Cell, 2011. 146 (5): p. 682-95.

[33]Speakman, J.R. and S.E. Mitchell, Caloric restriction. Mol Aspects Med, 2011. 32 (3): p. 159-221.

Paleo Diet Guide to Keep Your Gut Healthy for the Holidays | The Paleo Diet

The Holidays are a time for office parties and get-togethers with family and friends with sleigh-fulls of delicious holiday foods!

Between the list of to-do’s, to-buy’s, to-make’s, to-call’s, to-rsvp’s and merrymaking aplenty, it’s all too easy to run yourself dry and put your health last. Not only can this concession ruin your holiday season if you get sick, but it can inevitably lead to a whole NEW list of problems that will take you more than just January to recover from.

Bloating, headache, gas, constipation, diarrhea, indigestion…we’ve all had one or more of these.  That second helping of turkey and fixings, just another dessert or two. While we convince ourselves and each other it’s no big deal, our “second brain” is always watching.  Each bite. Each mouthful. Each swallow.

This “second brain”1 is the gut’s network of 100 million neurons sending information from the stomach, through the intestines. The gut decides what to digest, absorb, excrete and, sometimes, send back, making us violently sick in the process. Dr. Gershon2, author of The Second Brain, said it best, “The brain doesn’t like to micromanage; it leaves the details of digestion up to the gut.”

And the gut takes its job very seriously.

So how do we get through all the merrymaking and celebrations with our loved family and friends without weight gain, bloating, sugar crashes and digestion problems while still managing to enjoy ourselves?  By following a few tips and tricks.

7 SIMPLE TIPS TO GET YOUR BRAIN AND GUT IN GEAR

1. Drink Enough Water

Your first stop when you get up in the morning should be the sink.  Fill the biggest glass you have with lukewarm water and squeeze a lemon into it for 3 seconds.  Drink it all, and refill, drinking a second glass (or as much of it as you can).

The combination of lukewarm water and freshly squeezed acidic lemon juice3 first thing in the morning wakes up the gut gently and helps with the digestive processes throughout the day. It’s a small change in your routine and especially important through hectic weeks over the holidays.

2. Sleep

This is always on everyone’s list to staying healthy, but who’s got the time? Here’s a little secret; we always have enough time, it’s just a matter of how we choose to spend it. Make the choice to leave a little early from the party, to politely say no to that after work happy hour, or skip that last store on the shopping list.

When our bodies don’t get enough sleep it becomes harder to focus, to function and to digest.4 While one or two nights with less sleep might not seem like a big deal, each one takes a toll on our bodies.  And remember the gut knows it all.

3. 50% Rule

Forget every food chart and plate diagram you’ve ever seen. To keep your gut healthy, your body, and in turn yourself happy, make it a rule to always fill at least half your plate with veggies.

Vegetables are easy to digest and great sources of carbohydrates and calcium, keeping you full longer. Between the holiday festivities and platters of food, gravitate toward the veggie tray – it’s a perfect match.

4. Alkaline Foods

Think Broccoli, kale, sweet potatoes, apples, berries.

Emotional stress is all too common during the holidays, and when combined with sugary foods, grains and processed meats the body’s overall pH decreases from its ideal (7.4)5 making absorption of minerals and nutrients more difficult for the gut.

To combat the harmful acidic environment that this creates in the body, include alkaline greens such as spinach, dates, oranges and grapefruit in your diet at least 3-5 times/week.  An alkaline pH in the body minimizes inflammation in the gut and allows for optimal stomach and intestinal health and function.6

5. Artichokes

To keep that gut healthy throughout the Holidays, it’s important to keep the ‘good’ bacteria of the gut lining in check and flourishing.

Artichokes are a Paleo approved food that fall into a group called prebiotics.7 Prebiotics like artichokes, bananas also fall into this category, contain indigestible nutrients that help feed the beneficial bacteria in your gut.8 By adding artichokes into your holiday meals, you’ll keep those good bacteria well fed and your gut healthy and happy.

6. The ONE Dessert Rule

This category is unfortunately where we tend to over-indulge most frequently, and the one place that is just loaded with sugars, margarines and grains almost always sending our gut into agony.

Just say no to the pastry, pies, and the processed. While the Paleo Diet prescribes an 85:15 Rule allowing for the occasional cheat or Paleo treat, we say go for the fruit platter! You’ll still get a chance to sample a variety without the unnecessary digestive problems when your gut works overtime.

7. Think ‘Balance’

The hardest to stick to during the holidays – it is often the most important.

To keep digestive disorders and irritabilities at bay, try to make the time to exercise at least 3 times/week (a brisk 20 minute walk is better than nothing!).

This will let you just fly through numbers 1-6 and enjoy the Holidays without indigestion and gut-related stresses like bloating, constipation, diarrhea, acid reflux and all the rest. Because nobody wants those as surprise gifts at Christmas dinner.

Happy Holidays, All!

@PaleoWired
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Sanja JovanovicSanja Jovanovic is a co-founder of PALEO WIRED – a site dedicated to GATHER the best and latest paleo recipes & information to share with you, to inspire you to EAT the deliciousness of those recipes and creations and to REPEAT each day.  Because we’re all going to eat something anyway, might as well make it something that our bodies will thank us for!

REFERENCES

[1] Gershon, M. D. The Second Brain: A Groundbreaking New Understanding of Nervous Disorders of the Stomach and Intestine. New York: HarperCollins; 1998. 336p.

[2] Ibid.

[3] “Journal of Agricultural and Food Chemistry”; Metabolism of Antioxidant in Lemon Fruit (Citrus limon BURM. F.) by Human Intesetinal Bacteria; Yoshiaki Miyake et al.; 1997.

[4] Chen CL, Liu TT, Yi CH, Orr WC. Evidence for altered anorectal function in irritable bowel syndrome patients with sleep disturbance. Digestion. 2011;84(3):247-51. PMID: 21952561.

[5]Koziolek M, Grimm M, Becker D, Iordanov V, Zou H, Shimizu J, Wanke C, Garbacz G, Weitschies W. Investigation of pH and Temperature Profiles in the GI Tract of Fasted Human Subjects Using the Intellicap® System.  J Pharm Sci. 2014 Nov 19. PMID: 25411065.

[6] Lallès JP. Intestinal alkaline phosphatase: novel functions and protective effects. Nutr Rev. 2014 Feb;72(2):82-94. PMID: 24506153.

[7] Ramnani P, Gaudier E, Bingham M, van Bruggen P, Tuohy KM, Gibson GR. Prebiotic effect of fruit and vegetable shots containing Jerusalem artichoke inulin: a human intervention study. Br J Nutr. 2010 Jul;104(2):233-40. PMID: 20187995.

[8] Ibid.