Just Read: Triglycerides and Cardiovascular Disease – American Heart Association Scientific Statement

Yes, all 40+ pages of the American Heart Association’s scientific statement, published in 2011 (the most recent one – citation below), for leisure.


Triglycerides are that lipid component in our blood that we (or let’s say I) are trained not to pay that much attention to, especially relative to cholesterol (LDL, HDL, etc), and yet its story unlocks a lot of mysteries around nutrition and health (again, for me).

Jumping right in.

  • “It is especially disconcerting that in the United States, mean triglyceride levels have risen since 1976, in concert with the growing epidemic of obesity, insulin resistance (IR), and type 2 diabetes mellitus (T2DM).”
    • As much as we’re fighting LDL, we don’t seem to be winning on this one. Why? And does it matter? (several reasons, and yes)

The dyslipidemic triad and diabetes

High triglyceride levels that accompany either normal or impaired fasting glucose predict the development of Type 2 Diabetes,1and therefore, hypertriglyceridemic states should prompt surveillance to rule out T2DM. In addition, 35% of T2DM adults have fasting triglyceride levels > 200 mg/dL associated with decreased HDL-C and small, dense LDL particles.

Size matters – of LDL particles, that is

LDL particles in patients with DM may be atherogenic even at normal LDL-C concentrations..In addition, hypertriglyceridemia is associated with small, dense, and CE-depleted LDL particles. Thus, individuals with T2DM and mild to moderate hypertriglyceridemia exhibit the pattern B profile of LDL (smaller, denser particles) described by Austin and Krauss; these particles be more susceptible to oxidative modification and catabolism via macrophage scavenger receptors

That’s the not good thing that happens inside blood vessels that causes disease and it’s connected to triglycerides.

In other words (my interpretation), it’s not what triglycerides mean by themselves, it’s the pattern that they are connected to. And therefore, looking at just one number (LDL) has limitations to predict disease. On the other hand, focusing on LDL is easy to do and simple to understand…hence the need for this scientific statement to understand the biology better than most people probably do.

Continuing on.

How we got here. The low-fat diet aka SnackWells USA

The relationship between percent of total fat intake and change in triglyceride and HDL-C concentrations was reported in a meta-analysis of 19 studies published by the Institute of Medicine. In this analysis comparing low-fat, high-CHO diets versus higher-fat diets, for every 5% decrease in total fat, triglyceride level was predicted to increase by 6% and HDL-C to decrease by 2.2%

Overall, optimization of nutrition-related practices can result in a marked triglyceride-lowering effect that ranges between 20% and 50%. These practices include weight loss, reducing simple CHO at the expense of increasing dietary fiber, eliminating industrial-produced trans fatty acids, restricting fructose and SFA, implementing a Mediterranean-style diet, and consuming marine-derived omega-3 PUFA (Table 11). Dietary practices or factors that are associated with elevated triglyceride levels include excess body weight, especially visceral adiposity; simple CHOs, including added sugars and fructose; a high glycemic load; and alcohol.

And the American Heart Association recommended high carbohydrate diets and even candy in the prevention of cardiovascular disease. Oops.

For the biologists/scientists – how carbohydrates may result in higher triglycleride levels and unhealthy lipid profiles

Mechanistically, high CHO intake triggers pancreatic insulin release in response to increased blood glucose. Insulin, in turn, activates sterol regulatory element–binding protein, (SREBP-1c), a transcription factor that regulates fatty acid and triglyceride synthesis. Recently, 2 additional transcription factors, X-box binding protein 1 (XBP1) and CHO response element–binding protein (ChREBP), have been identified as inducers of hepatic lipogenesis in response to ingested CHOs (eg, fructose and glucose) that is independent of insulin.431,432 In contrast, unsaturated fatty acids reduce or inhibit SREBP-1c transcription, thereby reducing hepatic fatty acid synthesis430 and plasma triglycerides.

Using drugs to treat

However, in LIPID, although baseline triglyceride level was not signifi- cantly associated with CVD risk in patients given placebo, each 89-mg/dL decrease in on-treatment triglyceride level in patients given pravastatin significantly decreased CVD risk by 11%, as well as by 14% after adjustment for nonlipid risk factors. However, the lipid-related parameters most strongly associated with CVD risk in LIPID were apo B, LDL-C, and the ratio of TC to HDL-C

Again, the dyslipidemic triad.

Taken together, reductions of 50% or more in triglyceride levels may be attained through intensive therapeutic lifestyle change.

A low fat, high carbohydrate diet increases triglycerides and decreases HDL, the opposite, a higher fat, lower carbohydrate diet reduces triglycerides and increases HDL. For me this explains the non-sequitir of my pathology textbook in medical school stating that high carbohydrate diets are a risk factor for heart disease at the same time high carbohydrate diets were being recommended to prevent heart disease.

A discussion of statins is out of scope here – many many many, many many, articles already cover this.

Andrew Weil, MD’s advice to us in medical school – understand what you’re prescribing to your patients

…I think he may have said that we should try every drug we prescribe to understand its effects (with rationality of course) but human memory can be semi-faulty after so many years…either way it was something of a gift for him to be on faculty at my medical school (University of Arizona) because it promoted an embrace of curiosity that persists to this day, every day.

In any event, I’ve switched to a low carbohydrate diet over the past year. I’m not ready to share my personal health information here, but I will eventually. And my biology is tracking science, as expected, because, well, that’s how science works :).

More to come. In the meantime, here’s a helpful piece on the low-fat diet and what it has done for our health.

Citation: Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, et al. Triglycerides and Cardiovascular Disease. Circulation [Internet]. 2011 [cited 2016 Dec 25];123(20).

Just Read: What should people with diabetics eat? Study of a low-calorie ketogenic diet

Just catching up on my blogging and continuing a closer look at nutrition and health.

This paper discusses a different and emerging approach about diet in people with diabetes, beginning with the declaration that we really don’t know what the optimal diet for people with diabetic is:

The optimal degree of caloric restriction and macronutrient distribution of medical nutritional therapy in T2DM is not well defined.

Traditionally, a low-fat diet has been prescribed, which really is a high-carbohydrate diet that brings with it questions about why feeding carbohydrates to people who are intolerant of them makes sense.

In this intervention, subjects were divided and some were feed a ketogenic (higher fat, lower carbohydrate) diet. In medical school, we’re taught that ketones are a bad thing because of their association with a life-threatening condition known as keto-acidosis. However, in people who have some insulin left, ketones become an alternate fuel from the breakdown of fat.

The diet used here appears to be a little “engineered” compared to what I have read is also done, which is little to no calorie restriction.

And…the results show significant weight loss, glucose control, and as seen in other studies, a significant drop in triglycerides, that other under-emphasized lipid in our training (I’ll post on that later).

Interestingly, I ran across this medical practice based in San Francisco (@VirtaHealth) using this approach to achieve better outcomes in Diabetes. So, I suppose this is becoming a thing. With science attached to it, including its own published intervention trial.

Maybe we are set to really change the way we think about healthy eating….

Just Read: Listening to Physiology instead of a Wearable for Weight Loss

Comparison Wearable induced vs Physiologic  induced weight loss 161003
Comparison Wearable induced vs Physiologic induced weight loss 161003 (View on Flickr.com)

After reading the study about the impact of (a certain type of) wearable devices on weight loss (See: Just Read: Study – Wearables don’t improve weight loss – can you outrun a bad diet? ) – answer, not much – I also read this study at the same time that focused on exercise and diet in a very different way, and had much different outcomes.

In Mark S, Toit S Du, Noakes TD, et al. A successful lifestyle intervention model replicated in diverse clinical settings. South African Med. J. 2016;106(8):763. Available at: http://www.samj.org.za/index.php/samj/article/view/10136 [Accessed October 2, 2016], a few conventional and unconventional things were tried in a group of willing subjects interested in weight loss:

  1. Behavioral intervention – variable timeframe (conventional)
  2. Caloric restriction until the reaching of weight goal, including fat, sugar, refined cardohydrate restriction (conventional)
  3. NO moderate or vigorous exercise until weight goal achieved (UNconventional)
  4. HIGH fat diet after weight goal achieved (UNconventional>

Foods consumed on the maintenance diet included beef, poultry, fish, eggs, oils, moderate amounts of hard cheeses, and small amounts of nuts, nut butters, seeds and berries.

I can’t determine the actual time to follow-up for the groups, but it looks to be around 2 years, which is the same time as the group in the wearables study. Therefore, I charted the two groups (S1 and S2, for “site 1” and “site 2” in rural practices in British Columbia, Canada) along side the results of the subjects in the wearable study, above (click to enlarge).

Lots of caveats

  • The interventions were different, however both interventions involved manipulation of diet. For the wearables subjects, it was caloric restriction and low-fat (high carbohydrate). For the Canadian subjects it was caloric restriction initially, and then transition to high fat (low carbohydrate).
  • The populations are different, and the starting weights of the subjects makes it hard to compare % weight loss, although to my eyes, they started out pretty close in weight
  • Neither study controlled for diet, meaning there was no comparison group of people who didn’t have their diet manipulated

This is also the part where conflict of interest disclosures are important.

For the wearables article:

Conflict of Interest Disclosures: Dr Jakicic reported receiving an honorarium for serving on the Scientific Advisory Board for Weight Watchers International; serving as principal investigator on a grant to examine the validity of activity monitors awarded to the University of Pittsburgh by Jawbone Inc; and serving as a co-investigator on grants awarded to the University of Pittsburgh by HumanScale, Weight Watchers International, and Ethicon/Covidien. Dr Rogers reported serving as principal investigator on a grant awarded to the University of Pittsburgh by Weight Watchers International. Dr Marcus reported receiving an honorarium for serving on the Scientific Advisory Board for Weight Watchers International. No other disclosures were reported.

For the lifestyle intervention article:

Conflicts of interest. SDT, KN, DC, MM, SVDS and JF have no conflicts of interest to declare. SM is the founder of a sole proprietorship, Approach Analytics, providing analytical support to clinical and public health initiatives. JW is on the Scientic Advisory Board for Atkins Nutritionals Inc. and has accepted honoraria and travel expenses to attend meetings. TN is the author of the books Lore of Running and Waterlogged and co-author of e Real Meal Revolution, Raising Superheroes and Challenging Beliefs. All royalties from the sales of e Real Meal Revolution and Raising Superheroes and related activities are donated to the Noakes Foundation, of which he is the chairman and which funds research on insulin resistance, diabetes and nutrition as directed by its Board of Directors. Money from the sale of other books is donated to the Tim and Marilyn Noakes Sports Science Research Trust, which funds the salary of a senior researcher at the University of Cape Town, South Africa. The research focuses on the study of skeletal muscle in African mammals with some overlap to the study of type 2 diabetes in carnivorous mammals and of the e ects of (scavenged) sugar consumption on free- living (wild) baboons.

The unconventionality of the the intervention is mentioned in the article as something that was hard for others to accept:

Despite the rigour of our quality improvement process, our efforts to communicate the merits of this intervention to health system administrators met with a frustrating lack of uptake. This is not surprising, given that the research literature has many competing ‘solutions’ for the epidemics of obesity and diabetes,[15] many of which are difficult to falsify.[16]

From my understanding of the culture of medicine, something like this written in a scholarly article is usually a vast understatement.

The next several months/years are going to be exciting in this part of health, now that we have a better understanding of physiology and newer tools to (potentially) change our environment and our behavior (maybe).

Just Read: Study – Wearables don’t improve weight loss – can you outrun a bad diet?

I stopped wearing a fitness tracker because it DEmotivated me, by reminding me of the times I was not meeting my activity goals

This is what an attendee said at the recent convening on Making Health Care Measurement Patient-Centered (a proxy for respecting people in health care).

This study published in JAMA a few weeks ago (September, 2016), produced unexpected (and curious) results.

Overweight and obese younger people randomized to receive wearable devices as part of a weight loss program gained back more weight than users who did not receive wearables, after an initial 6 month weight loss.

Both sets of subjects did not have significantly different rates/intensity of physical activity over the 2 year study, and their dietary intake was not statistically significant from each other (calories taken in slightly less for the wearables group at the end). Specifically, the group with the wearable did not exercise more than the group without the wearables.

I was of course curious and decided to look more closely at the data. I produced some charts below.

Here are the things I noticed

  • Subjects were randomized at the very beginning of the study, not at the 6 month mark, when the wearables were initiated. Did they know which group they were in at the beginning and did this shape their behavior?
  • I ask the question above, because the one thing I noticed in charting the data is that the group with the wearables (EWLI – stands for “Enhanced Weight Loss Intervention”), experienced a visible plunge in MVPA: “Nonsupervised moderate-to-vigorous physical activity” even before they got the wearables, that continued well past the time they had the wearables. Overall, though, across the 24 months, there was not found to be a significant difference in physical activity.
  • The subjects were placed on what are essentially high carbohydrate diets with caloric restriction, which remained restricted throughout the 24 months.

Outrunning a bad diet?

I was recently introduced to the work of Tim Noakes (@ProfTimNoakes) (about 5 years behind the rest of the world, but maybe 1-2 years ahead of part of the world) and decided to look more closely at other factors.

Focusing on the diet of the subjects, here’s what it said in the study details (supplemental materials)

All subjects will be prescribed an energy restricted dietary intervention that we have shown to effectively reduce body weight by 8-10% within the initial 6 months of treatment. This will include reducing energy intake to 1200 to 1800 kcal/d based on initial body weight (<200 pounds = 1200 kcal/d; 200 to 250 pounds = 1500 kcal/d; >250 pounds = 1800 kcal/d). Data from our research studies [14, 15] and the National Weight Control Registry [26] indicated that macronutrient composition in the most successful participants consists of 20-30% dietary fat intake, 50-55% carbohydrate intake, and 20-25% protein intake. Therefore, a similar dietary composition will be recommended in this study. However, we do recognize that low carbohydrate/high protein diets are currently popular, have demonstrated some initial efficacy, and some participants may gravitate towards this macronutrient composition, and this will be acceptable provided that total energy intake is within the prescribed range. To facilitate the adoption of the dietary recommendations, individuals will be provided with meal plans (see Appendix B), that will allow them to plan for modifications in their daily and weekly meal plans, and a calorie counter book.

So they were permitted to lower their carbohydrate intake as long as they maintained the same amount of calorie restriction. As a group they did not do this, though. They stuck to their high carbohydrate diets over the long run.

From this paper:

Malhotra A, Noakes T, Phinney S. It is time to bust the myth of physical inactivity and obesity: you cannot outrun a bad diet. Br. J. Sports Med. 2015;49(15):967–8.

Regular physical activity reduces the risk of developing cardiovascular disease, type 2 diabetes, dementia and some cancers by at least 30%. However, physical activity does not promote weight loss.

And there was the September 12, 2016 cover story of Time Magazine:

For all its merits, however, exercise is not an effective way to lose weight, research has shown. In a cruel twist, many people actually gain weight after they start exercising, whether from new muscle mass or a fired up appetite.

This study is about wearables, not exercise, because both groups of people exercised about the same over time.

However, because both groups were on a high-carbohydrate diet throughout the intervention, it’s possible that even if the wearables “worked” (they exercised more), that the results would be the same.

Still pro exercise…

I, like Bob Sallis, MD, who is quoted in the Time magazine article, support exercise for the numerous health benefits it offers – just look up any of my presentations on the topic, oh like this one:

Presentation/Photos: Quantified Community, Population Sensors at WalkHackNight, Transportation Techies

What if listening to a wearable device isn’t as effective as listening to your body? I’m going to post on another approach tomorrow….

Charts from Effect of Wearable Technology on Weight Loss
Charts from “Effect of Wearable Technology Combined With a Lifestyle Intervention on Long-term Weight Loss. JAMA. 2016;316(11):1161.” (View on Flickr.com)