The Paleo diet and other high-protein diets may be among the more harmful popular diets recommended for weight loss because they:
• raise blood levels of TMAO, a marker for increased heart attack risk (European Journal of Nutrition, July 5, 2019:1–14), and
• fail to lower high blood sugar even when they promote weight loss ((Evid Based Med, 2013;18(4):e37). Weight loss almost always lowers high blood sugar levels except when a person eats a very high-protein diet.

Paleo Diet and the Microbiome
The Paleo-type diets usually recommend that you eat lots of meat, and avoid grains and legumes. Both eating meat and restricting soluble fiber (in grains and beans) markedly increase the growth of the harmful bacteria that cause higher blood levels of TMAO. These harmful types of bacteria in the colon produce the chemical TMA that is converted to TMAO, which causes inflammation that can lead to heart attacks and certain cancers. Researchers at Edith Cowan University in Australia followed 44 people on a Paleo diet and 47 on a traditional Australian diet for one year (European Journal of Nutrition, July 5, 2019:1–14). They found that people who were on the Paleo diet had:
• lower levels of healthful colon bacteria,
• higher levels of the harmful colon bacteria that produce TMAO,
• lower levels of healthful short chain fatty acids (SCFAs), and
• double the blood levels of TMAO.
The same authors had previously put people on a Paleo diet for four weeks and did not find increased levels of TMAO (British Journal Of Nutrition, Nov 2018;121(3):1-14). They were severely criticized for that four-week study so they repeated the study for one year and found the marked increase in TMAO.

Restricting whole grains and beans can also increase heart attack risk because it deprives you of some of the best sources of soluble fiber, which appears to be one of the most important components of a healthful diet. Soluble fiber is not absorbed in your upper intestinal tract. The soluble fiber passes to your colon where healthful bacteria convert it into short chain fatty acids (SCFAs) that lower inflammation, high blood sugar, high blood pressure and high cholesterol to help prevent heart attacks, cancers and other diseases (J Atheroscler Thromb, July 1, 2017;24(7):660–672).

High Blood Sugar Not Reduced by Paleo Diet
A major benefit of losing excess weight is that it increases insulin sensitivity that lowers high blood sugar levels, which reduces your chances of becoming diabetic and suffering a heart attack. High-protein weight-loss programs do not increase insulin sensitivity as much as normal-protein diets do, and therefore do not prevent diabetes as effectively as diets that are not high in protein (Evid Based Med, 2013;18(4):e37). Weight loss that comes with reasonable amounts of protein makes your cells more sensitive to insulin and therefore insulin becomes more effective in lowering high blood sugar levels.

High-protein diets do not improve insulin sensitivity, and do not help dieters retain significantly more muscle than those on a low-protein diet. Eating extra protein when you are trying to lose weight does not prevent loss of muscle size and strength significantly more than any other weight-loss diet (Journal of Sports Sciences, 2004;22(1)). When a person loses weight, two-thirds of weight loss is usually fat and one third is lean tissue including muscle. The low-protein dieters lost a statistically insignificant fraction of muscle weight more than the high-protein, low-carbohydrate dieters. Eating a high protein diet with a lot of meat, fish and chicken (high protein) and limiting carbohydrates does not improve insulin sensitivity, even though it can help you to lose weight.

Insulin Insensitivity
Most cases of diabetes in North America are caused by insulin insensitivity, in which cells are not able to respond to insulin, so the pancreas keeps on putting out more insulin and blood insulin levels rise very high, which increases risk for certain cancers. When you get rid of fat from your body, you are supposed to improve your sensitivity to insulin, and lower insulin levels and blood sugar. However, when you lose weight by eating lots of protein-rich foods, you raise insulin levels just as you do when you take in lots of sugary foods. High insulin levels are associated with increased risk for heart attacks and certain cancers.

Insulin does a lot more than just lowering high blood sugar levels. Insulin drives certain amino acids from protein into cells (Diabetes Res Clin Pract, August 2011;93(Suppl 1):S52-9), so your pancreas releases insulin to lower high blood protein levels as well as high blood sugar levels. Excess insulin drives the extra protein building blocks into your liver where they are converted to fat, which fills the liver with fat. A fatty liver cannot accept much sugar from your bloodstream, so blood sugar levels remain high to damage all the cells in your body and increase your risk for diabetes.

Insulin and Fatty Liver
When blood sugar levels rise, the pancreas releases large amounts of insulin which lower high blood sugar levels by driving sugar from the bloodstream primarily into the liver. Fat in the liver prevents the liver from accepting this sugar and blood levels rise even higher. High rises in blood sugar can damage cells throughout your body. When you lose weight, you get fat out of your liver, so your liver can then effectively pull sugar out of the bloodstream. The high-protein diet increases insulin levels, and insulin converts sugar to fatty triglycerides to increase deposition of fat in the liver. I think this is one of the reasons why elite body builders and competitive athletes in sports requiring great strength are at a markedly increased risk for dying from heart attacks and diabetes (J of Urology, April, 2016;195(4Supplement):e633).

My Recommendations
If you are trying to lose weight, I think you should avoid all of the popular high-protein diets such as Paleo, Atkins, and Dukan. Eat plenty of carbohydrates as nature made them: vegetables, whole (unground) grains, beans, nuts and other seeds. Restrict refined carbohydrates: sugar-added foods, sugared drinks including fruit juices, and foods made from flour such as bakery products, pastas, and most dry breakfast cereals. Eat a reasonable amount of protein.

Eating lots of high-protein foods does not help athletes grow larger muscles than when they take in moderate amounts of protein. High protein diets do not make your cells more sensitive to insulin, so they are less likely than normal-protein diets to help prevent diabetes. Almost all weight loss strategies other than the high-protein diets will help to increase insulin sensitivity and to prevent diabetes. I recommend a Mediterranean-type diet and intermittent fasting.