Intermittent fasting with a high-protein diet mitigated osteoarthritis symptoms by increasing lean body mass and reducing inflammation in osteoarthritic rats with Alzheimer’s disease-like dementia

Abstract

Menopausal women are susceptible to osteoarthritis and memory impairment. We hypothesized that Alzheimer’s-like disease (AD) exacerbates osteoarthritis and that intermittent fasting(IMF) with a high-protein(H-P) diet would enhance memory function and relieve osteoarthritis symptoms in estrogen-deficient animals with surgically induced AD and osteoarthritis. The action mechanism was also explored. Ovariectomized Sprague-Dawley rats were fed high-fat(H-F) or H-P diets for two weeks, and then they had a hippocampal infusion of β-amyloid(25-35) for 4 weeks to induce AD and an injection of monoidoacetate(MIA) into the articular cartilage to induce osteoarthritis. Four groups had AD symptoms, whereas two groups had non-AD symptoms by hippocampal amyloid-β(35-25) infusion. All rats had an MIA injection into the articular cartilage of the left knee. IMF suppressed memory impairment in AD rats, especially those fed H-P diets. Compared to Non-AD, AD exacerbated osteoarthritis symptoms, including swelling, limping, slowed treadmill running speed, and uneven weight distribution in the left leg. The exacerbations were linked to increased inflammation and pain, but IMF and H-P lessened inflammation and pain-related symptoms. Lean body mass(LBM) also decreased with AD and IMF, but H-P protected against LBM loss. Histological examination of the knee joint revealed the degree of the cellular invasion into the middle zone, and the changes in the tidemark plateau were greatest in the AD-AL with H-F, while non-AD-IMF improved the cellular invasion to as much as non-AD-AL. H-P reduced the infiltration into the middle-zone of the knee and promoted collagen production. In conclusion, AD exacerbated the articular cartilage deterioration and memory impairment, and IMF with H-P alleviated the memory impairment and osteoarthritic symptoms by decreasing hippocampal amyloid-β deposition and proinflammatory cytokine expressions and by increasing LBM.

Polygenetic Variants Related to Osteoarthritis Risk and Their Interactions with Energy, Protein, Fat, and Alcohol Intake in Adults in a Large Cohort

“…OA risk is affected by lifestyle, but few regimes efficiently prevent or reduce the it [ 31 ]. Fish oil, protein, dietary fiber, and polyphenols, including curcumin, are recommended to improve OA symptoms [ 32 , 33 , 34 , 35 ]. On the other hand, their efficacy is varied and controversial [ 36 ].…”

“…OA risk is closely related to obesity, and weight loss is recommended for reducing OA symptoms. Intermittent fasting is one weight-loss method and OA therapy [ 33 ]. The present study showed that PRS interacted with dietary intake, including energy, protein, fat, and alcohol, to influence OA risk, even though dietary intake did not affect OA risk.…”

Sarcopenia Is a Cause and Consequence of Metabolic Dysregulation in Aging Humans: Effects of Gut Dysbiosis, Glucose Dysregulation, Diet and Lifestyle

“…However, calorie restriction does not maintain or increase skeletal muscle mass, although it does maintain muscle strength [109]. Nevertheless, intermittent fasting has been reported to reduce fat mass and maintain or increase skeletal muscle mass by ameliorating oxidative stress and decreasing proinflammatory cytokines in human and animal studies [110][111][112][113]. Intermittent fasting reduces body fat mass, insulin resistance, and proinflammatory cytokines in adults; it also induces significant changes in gut microbiota communities, increases the production of short-chain fatty acids, and decreases the circulating levels of LPS in adults [110].…”

“…After intermittent fasting, the relative abundances of Ruminococcus gnavus, Chitinophagaceae bacterium, Roseburia faecis, Paraburkholderia caribensis, Verrucomicrobiae bacterium Ellin516, Neisseria dentiae, and Streptococcus ferus increase [110]. Intermittent fasting modulates gut microbiota to increase Lactobacillales and decrease Clostridales in Alzheimer's disease-induced rats [111]. Therefore, intermittent fasting with a high protein diet may help maintain or increase skeletal muscle mass while modulating gut microbiota.…”

Protection against Osteoarthritis Symptoms by Aerobic Exercise with a High-Protein Diet by Reducing Inflammation in a Testosterone-Deficient Animal Model

“…As the normal control, male rats were given a sham-ORX operation by rubbing the testicles but not removing them. After the eighth week from the ORX or sham surgery, MIA (4 mg/50 µL saline; Sigma Co., St. Louis, MO, USA) was injected into the intra-articular cartilage through the patellar ligament of the left knee after anesthetizing them with intramuscular injections of a ketamine and xylazine mixture (100 and 10 mg, respectively) [15,16].…”