Caveman Doctor has been a follower of a Caveman/Paleo diet for quite some time now (a couple million years) and after the advent of reading, writing, and the internet, there has been a wealth of material published on inflammation, avoiding inflammation, and eating foods that fight inflammation. Caveman Doctor has always assumed that the foods he ate fought inflammation (why else would nature provide him with them?). However, he was recently writing up a diet protocol for his cancer patients in which they undergo a low-carbohydrate diet during treatment. One of the nutritionists asked Caveman Doctor how he was going to explain feeding people saturated fat instead of carbohydrates. He replied “with scientific data”. The nutritionist then told Caveman Doctor that the big issue with saturated fats is that they cause inflammation, and Caveman Doc would have to answer to his critics when they brought this up. So does saturated fat cause inflammation and does Caveman Doctor have some explaining to do?
Which Are Inflammatory: Fats or Carbohydrates?
The benefit of avoiding inflammation (and defending against it with antioxidants) is a recurring theme on this site. Inflammation is a hallmark of disease, ranging from damage to arteries, cancer, and a decreased immune system.
It also seems like everywhere you look nowadays, someone is blaming foods for being inflammatory. The low-carbers and Paleo/modern cavemen often put the blame on carbs, especially grains and sugar, while the conventional low-fat dieters throw the blame on fat. It’s interesting that the dietician above immediately pointed to saturated fat as the main cause of inflammation, while cancer patients often consume massive amounts of simple sugars in an effort to “keep weight” and nobody bats an eye. It seems like fat causes a knee-jerk negative reaction, while simple carbohydrates elicit much less emotion. So which side is right?
First Up: The Postprandial Studies
A large amount of studies exist looking at food and inflammation immediately after eating (the postprandial state: post = after, prandial = eating). Most take blood from participants at certain time intervals after a meal. The studies are plentiful, and running through them all would serve no real purpose other than supplying you with a good method to fall asleep.
However, here are three prime examples:
- Saturated Fat/Protein: A group of scientists looked at a high saturated fat or protein (casein) meal and found that they both caused inflammation1. Of note, there is a significant amount of literature showing casein protein to be inflammatory and Caveman Doctor goes for whey instead.
- Glucose: The same group looked at blood samples in participants after consuming pure glucose. Participants experienced an increase in reactive oxidative species or ROS generation and amount of ROS, and a decrease in the body’s defense of free radicals with lower alpha-tocopherol (vitamin E) levels2. ROS are oxidative compounds that damage cells.
- Mixed: A third study by this group fed participants egg-muffin and sausage-muffin sandwiches and 2 hash browns (81 g carbohydrate, 51 g fat, and 32 g protein), which (surprise, surprise) caused an increase in inflammation3. Let’s just ignore the fact that they fed them muffin sandwiches for the sake of the argument.
In conclusion, immediately after consumption:
- Glucose causes inflammation
- Fats cause inflammation
- Protein and fats cause inflammation
- As is the case often in the field of nutrition, there are studies that support any conclusion you want to make about food and inflammation.
The results of these studies lead us to two possible conclusions:
- All food except for air causes inflammation, and air probably does too (from its oxygen content…).
- All food can be shown to cause a transient increase in inflammation depending on your experimental constraints and we need to look at long-term studies.
Perhaps basically any food is going to cause a transient rise in inflammation, especially because nearly all food contains a small amount of bacteria and is a foreign element entering the body. Therefore, let’s take a closer look at number 2 and review some long-term studies.
Next Up: Do Population Studies Give Us More Insight?
Next up the ladder are studies following cohorts of people to see what associations exist with carbohydrates, fat, and inflammation. While these studies are generally fraught with error and one must be cautious with any large conclusions, they at least give us some hypothesis generation.
More Complex Carbs and Inflammation:
- A Dutch group and the group at Harvard looked at 18,000 women with food questionnaires (which are a horrendous method as discussed here), but it’s still at least worth giving it a look. Their results showed that as we move from low to high glycemic index carbohydrates (like bread and simple sugars) more inflammation and CRP is produced4,5.
- A similar study showed that high fiber intake (which slows digestion and blunts insulin release) appeared to lower TNF and IL-6 markers of inflammation, but had no effect on CRP6.
- Another study compared carbohydrates sources and found that wheat, potatoes, and oats actually up-regulated inflammatory genes7, while switching to carbohydrates with lower glycemic loads (which cause less insulin release) apparently reduces CRP8.
- As a side note, similar studies have showed that omega-3 fats were found to decrease CRP and inflammation9 and raise anti-inflammatory markers in the serum10.
The results are interesting, but not surprising. The negative health effects of simple sugars are more universally accepted by both ends of the nutritional science spectrum these days. It’s interesting to note that most of these studies were all looking at consuming different types of carbohydrates, and it appears that the further we hedge from foods that increase insulin (higher glycemic index), the less inflammation we cause.
The obvious questions that come to mind:
- Do only simple carbs cause inflammation or are all carbs pro-inflammatory?
- What happens when we limit all foods that increase insulin?
- What happens when we go on low-carb diets?”
We can scratch the surface by looking at the other factors involved, like obesity and insulin resistance
There are clearly many other factors involved, and narrowing it down simply to carbs or fat as the cause of inflammation is difficult. Other studies examined fat tissue in patients and found that inflammation was actually proportional to insulin sensitivity11,12, and population studies made similar conclusions13, putting the onus back on insulin and carbohydrates. This makes sense, as carbs directly affect insulin levels in our body. Studies have also shown that having high liver fat content is also associated with increased inflammation. Interestingly, there is ample data showing that a low-carbohydrate diet decreases liver fat content14. We also already know that CLA, a fat found in products from ruminant animals, like cows, is an anti-inflammatory compound.
What Does Metabolic Syndrome Have to Do with Inflammation?
When fed a high load of carbohydrates resulting in spikes in blood sugar, our bodies secrete insulin. If insulin levels remain excessively high for too long of a period, our body eventual becomes insulin resistant. If severe enough, this can lead to diabetes and eventually the need for medical insulin replacement.
During insulin resistance, the following happens:
- Fat cells convert to storage mode instead of burning fat
- Fat accumulation and weight gain occurs (starting centrally in the belly)
- Fat in the liver builds up (as it turns blood sugar into fat)
- Serum triglycerides increase (related to the liver)
- “Good” HDL decreases
- Blood pressure rises
These all happen to also be components of the metabolic syndrome. However, number seven not from the list above happens next: inflammation. The stress placed on our body from these insults creates a chronic stress, just like as we defined in Stress: The Basics, which we know results in an improper immune system response, and ultimately, inflammation. This is why scientists found that increased consumption of refined sugars and starches independently predicted for a greater risk of inflammatory death15. This entire process of several diseases is driven by insulin.
Other work puts the crosshairs back on carbohydrates as it shows that high blood sugar (hyperglycemia) after a meal is related to inflammation and oxidative stress16. Even PET scans, which measure inflammation, have shown increased amounts in the arteries of patients with impaired glucose tolerance and in diabetics17, both of which have high levels of serum glucose and insulin.
How Do These Studies Apply to Modern Cavemen?
The elephant in the room for most readers of this site is the question of who were the patients in these studies. I recently had a long conversation with my good friend and former college roommate Cliff Hodges, who runs Crossfit West in Santa Cruz. We were discussing how we often feel that some labs and lab values barely apply to modern cavemen. If you follow a Caveman/Paleo diet and lifestyle, you are likely healthier than 99.9% of the population out there and you also eat a relatively low-carbohydrate diet, so none of these studies may pertain to you. Paleo dieters and modern cavemen may need to view a different set of studies to take place in a cohort of people who follow these diets, but I am not going to hold my breath for that to happen.
What actually happens when a person eats a low-carbohydrate Caveman/Paleo type diet?
We know that carbohydrates increase insulin, the root of all evil when it comes to dieting and health, and rises in insulin lead to weight gain and a plethora of chronic diseases. But do carbohydrates lead to our other enemy, inflammation?
If you ask this to most doctors, dieticians, and health professionals, the answer would be we just don’t have the data (I know this because I asked doctors, dieticians, and health professionals).
Well luckily this isn’t the case, and we have people like Dr. Jeff Volek who has produced some well-designed low-carbohydrate studies. His team placed 40 overweight men and women on a low-carbohydrate or low-fat diet for 12 weeks. Of course the low-carbers lost significant weight (as they nearly always do in randomized studies). However, six markers of inflammation, including TNF and IL-6 (2 of our favorites) underwent a greater decrease in the low-carb dieters compared to the low-fat group18.
His group also showed, in a randomized-controlled trial, that a low-carbohydrate diet increases insulin sensitivity by 55%19. In this study they also looked at 16 biomarkers of inflammation, and every single one decreased. Six of these were significantly lower than the low-fat, high carb diet (which showed no benefit in any of the 16 markers).
Another six-month study compared a low-carb and low-fat diet and found that the low-carb diet significantly lowered CRP in high risk patients20.
However, Dr. Volek and his group also looked at retinol binding protein-4 (RBP4), which is a recently identified inflammatory adipokine. They found that a low-carbohydrate diet lowered RBP4 levels by 20%, while a low-fat diet increased them by 5%19. Marker levels correlated with carbohydrate amount consumed.
The long-term, randomized trials provide us with level 1 evidence that it’s highly likely that carbohydrates, and not fat, cause inflammation.
Does Saturated Fat Even Matter if You Are Low-Carb?
A controversial study looked at slightly increased saturated fat versus monounsaturated fat (like olive oil) in overweight subjects. They found that the saturated fat expressed more genes that regulate inflammation21. However, this fat was given with a high carbohydrate diet, which we know results in high levels of insulin to overweight patients, with a slew of other health problems, so these results do not add much clarity. This, of course, is ignoring the fact that saturated fats should in theory introduce less oxidation and inflammation into the body, since, unlike unsaturated fats, it will have much less space for free radicals to bind since it’s backbone is saturated with no double bonds (see here for a longer description).
Dr. Volek’s group also looked at whether the amount of saturated fat we eat on a low-carb diet actually ends up floating around in our blood. In his study, he compared the blood levels of saturated fat in 2 low-carb diet groups, one eating double the amount of saturated fat versus the other22. When he looked at the serum levels of saturated fat in the participants, there was no difference. Why did this happen? Likely, when there is no insulin around because there are no carbs around to stimulate it, we breakdown the saturated fat and use it for energy. The study by this group mentioned above18 found that the low-carb group ate three times the saturated fat as the low-fat group, but was found to have less saturated fats circulating in the blood. If insulin isn’t present, our fat cells turn off fat production and turn on lipolysis (fat breakdown).
Perhaps regardless of whether saturated fats are inflammatory or not, if consumed in the presence of a low-carbohydrate caveman-like diet, it may not even matter.
Dr. Volek summed it up quite nicely with his quote:
“This clearly shows the limitations of the idea that ‘you are what you eat’. Metabolism plays a big role. You are what your body does with what you eat.”23
Obesity and Insulin Resistance
One final point to note is how inflammation plays out in obese versus fit modern cavemen. Fat cells (adipocytes) in the face of insulin resistance create adipokines, which are inflammatory mediators like TNF, IL-6 the same inflammatory markers that are increased from stress. While these are present in insulin resistance, they also cause further elevated levels of blood sugar, creating a difficult cycle of high blood sugar and inflammation24. This pattern, part of the infamous metabolic syndrome, is effectively and efficiently corrected through a low-carbohydrate diet, but for some apparent reason our health “leaders” try fixing the problem of too much sugar and insulin with, well, more sugar and insulin.
This is when things start to get a little interesting. When obese and non-obese participants were given a high-fat, high-carbohydrate meal, and inflammatory free radicals were measured at several time intervals afterwards, measurement of free radicals returned to normal in the non-obese group, but remained high after 3 hours in the obese participants25. This data revisits the issue with applying these studies to lean modern caveman: perhaps in the short term, inflammation isn’t a factor of what eat, as long as we are normal weight?
Addressing this issue, another study put 29 obese patients on a very low-calorie diet (starving them at 800 calories per day) and compared their gene expression with that of non-obese subjects, before and after 28 days of intense weight loss. After the patients lost significant amounts of weight and fat tissue, they exhibited both a decrease in inflammatory gene markers, as well as an increase in anti-inflammatory molecules resembling that of the non-obese group26. Interestingly, as most of the inflammatory-causing genes are expressed in adipose tissue, this study seems to point more towards overall weight as having the effect on inflammation – and we all know which diet causes less weight gain.
These data emphasize the importance of having limited amounts of excess adipose tissue, and favoring low-carb diets as they have continually shown their superiority of fat loss in randomized trials. If you don’t have the tissue (adipose in this case) that creates the inflammation, you are curbing it before it happens.
Let’s Add This All Up:
- Carbohydrates and their increase in insulin lead to metabolic syndrome
- Low carbohydrate diets are a proven cure of type 2 diabetes and metabolic syndrome
- Metabolic syndrome leads to inflammation
- Having more adipose tissue leads to inflammation
- Having more stomach fat leads to inflammation
- Insulin turns off fat breakdown and stimulates fat production
- A low-carbohydrate diet has been proven time and time again to be optimal for reducing fat
- Adding this all up, it seems like how you view inflammation is actually more important than which foods study participants are eating.
- Obesity and metabolic syndrome is king when it comes to inflammation – avoid these as your first step. Everyone has a different way of accomplishing this, and I have seen the best in myself and others by eating the same foods we have eaten for millions of years.
- If you are eating a low-carb diet, foods that cause inflammation in the typical American diet may not lead to similar results in you.
- If you think the question lies in inflammatory markers immediately after eating, take your pick as to which foods cause inflammation because there is data to support them all.
- If you think it is more important to look at long-term studies, data is limited, but randomized controlled trials appear to favor a low-carb, high-fat diet.
I tend to favor well-designed randomized-controlled trials to get my dietary recommendations, and the data points to a high carbohydrate diet as the likely culprit of inflammation. Though frankly, saturated fat consumption may not even matter as in the face of a low-carb diet and low insulin levels, we clearly process it differently. Finally, let’s look at it like a cavemen:
Carbs cause insulin.
Insulin causes your body to store fat.
Stored fat promotes inflammation.
What more do we need to convict carbohydrates of the metabolic crimes they continue to commit?
1. Mohanty P, Ghanim H, Hamouda W, et al: Both lipid and protein intakes stimulate increased generation of reactive oxygen species by polymorphonuclear leukocytes and mononuclear cells. The American Journal of Clinical Nutrition 75:767-772, 2002
2. Mohanty P, Hamouda W, Garg R, et al: Glucose Challenge Stimulates Reactive Oxygen Species (ROS) Generation by Leucocytes. Journal of Clinical Endocrinology & Metabolism 85:2970-2973, 2000
3. Aljada A, Mohanty P, Ghanim H, et al: Increase in intranuclear nuclear factor κB and decrease in inhibitor κB in mononuclear cells after a mixed meal: evidence for a proinflammatory effect. The American Journal of Clinical Nutrition 79:682-690, 2004
4. Levitan EB, Cook NR, Stampfer MJ, et al: Dietary glycemic index, dietary glycemic load, blood lipids, and C-reactive protein. Metabolism: clinical and experimental 57:437-443, 2008
5. Du H, van der A DL, van Bakel MM, et al: Glycemic index and glycemic load in relation to food and nutrient intake and metabolic risk factors in a Dutch population. The American journal of clinical nutrition 87:655-661, 2008
6. Ma Y, Hébert JR, Li W, et al: Association between dietary fiber and markers of systemic inflammation in the Women’s Health Initiative Observational Study. Nutrition (Burbank, Los Angeles County, Calif.) 24:941-949, 2008
7. Kallio P, Kolehmainen M, Laaksonen DE, et al: Dietary carbohydrate modification induces alterations in gene expression in abdominal subcutaneous adipose tissue in persons with the metabolic syndrome: the FUNGENUT Study. The American journal of clinical nutrition 85:1417-1427, 2007
8. Neuhouser ML, Schwarz Y, Wang C, et al: A Low-Glycemic Load Diet Reduces Serum C-Reactive Protein and Modestly Increases Adiponectin in Overweight and Obese Adults. The Journal of nutrition 142:369-374, 2012
9. Lopez-Garcia E, Schulze MB, Manson JE, et al: Consumption of (n-3) Fatty Acids Is Related to Plasma Biomarkers of Inflammation and Endothelial Activation in Women. The Journal of Nutrition 134:1806-1811, 2004
10. Ferrucci L, Cherubini A, Bandinelli S, et al: Relationship of plasma polyunsaturated fatty acids to circulating inflammatory markers. The Journal of clinical endocrinology and metabolism 91:439-46, 2006
11. Westerbacka J, Cornér A, Kolak M, et al: Insulin regulation of MCP-1 in human adipose tissue of obese and lean women. American Journal of Physiology – Endocrinology And Metabolism 294:E841-E845, 2008
12. Bruun JM, Stallknecht B, Helge JW, et al: Interleukin-18 in plasma and adipose tissue: effects of obesity, insulin resistance, and weight loss. European Journal of Endocrinology 157:465-471, 2007
13. Festa A, D’Agostino R, Howard G, et al: Chronic Subclinical Inflammation as Part of the Insulin Resistance Syndrome : The Insulin Resistance Atherosclerosis Study (IRAS). Circulation 102:42-47, 2000
14. Browning JD, Baker JA, Rogers T, et al: Short-term weight loss and hepatic triglyceride reduction: evidence of a metabolic advantage with dietary carbohydrate restriction. The American Journal of Clinical Nutrition 93:1048-1052, 2011
15. Buyken AE, Flood V, Empson M, et al: Carbohydrate nutrition and inflammatory disease mortality in older adults. The American Journal of Clinical Nutrition, 2010
16. Ceriello A, Bortolotti N, Motz E, et al: Meal-induced oxidative stress and low-density lipoprotein oxidation in diabetes: the possible role of hyperglycemia. Metabolism: clinical and experimental 48:1503-8, 1999
17. Kim TN, Kim S, Yang SJ, et al: Vascular Inflammation in Patients with Impaired Glucose Tolerance and Type 2 Diabetes: Analysis with 18F-Fluorodeoxyglucose Positron Emission Tomography. Circulation: Cardiovascular Imaging, 2010
18. Forsythe C, Phinney S, Fernandez M, et al: Comparison of Low Fat and Low Carbohydrate Diets on Circulating Fatty Acid Composition and Markers of Inflammation. Lipids 43:65-77, 2008
19. Volek J, Phinney S, Forsythe C, et al: Carbohydrate Restriction has a More Favorable Impact on the Metabolic Syndrome than a Low Fat Diet. Lipids 44:297-309, 2009
20. Seshadri P, Iqbal N, Stern L, et al: A randomized study comparing the effects of a low-carbohydrate diet and a conventional diet on lipoprotein subfractions and C-reactive protein levels in patients with severe obesity. The American journal of medicine 117:398-405, 2004
21. van Dijk SJ, Feskens EJ, Bos MB, et al: A saturated fatty acid–rich diet induces an obesity-linked proinflammatory gene expression profile in adipose tissue of subjects at risk of metabolic syndrome. The American journal of clinical nutrition 90:1656-1664, 2009
22. Forsythe C, Phinney S, Feinman R, et al: Limited Effect of Dietary Saturated Fat on Plasma Saturated Fat in the Context of a Low Carbohydrate Diet. Lipids 45:947-962, 2010
23. Low-carb Diet Reduces Inflammation And Blood Saturated Fat In Metabolic Syndrome., Suny Downstate Medical Center. Science Daily, 2007
24. Volek JS, Phinney SD, Forsythe CE, et al: Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet. Lipids 44:297-309, 2009
25. Patel C, Ghanim H, Ravishankar S, et al: Prolonged Reactive Oxygen Species Generation and Nuclear Factor-κB Activation after a High-Fat, High-Carbohydrate Meal in the Obese. Journal of Clinical Endocrinology & Metabolism 92:4476-4479, 2007
26. CLÉMENT K, VIGUERIE N, POITOU C, et al: Weight loss regulates inflammation-related genes in white adipose tissue of obese subjects. The FASEB Journal 18:1657-1669, 2004
© Caveman Doctor 2012. All Rights Reserved